AuthOr’s VIew AuthOr’s VIew

The immune system is an important player in the treatment of non-muscle invasive bladder cancer, as evidenced by the fact that intravesical bacillus Calmette-Guérin (BCG) therapy has been the gold standard therapy for this type of disease for more than 3 decades. In many tumor types, studies have reported on varying asso-ciation between tumor cells and immune cells such as tumor associated macro-phages (TAMs), tumor-associated neu-trophils (TANs), tumor-associated T cells (TATs). All these immune cells behave in a context-specific manner, and can indeed exert both pro-tumor and anti-tumor functions. It has been postulated that nor-mal circulating neutrophils are of the N1 type (capable of attacking cancer cells), whereas in the tumor microenvironment neutrophils acquire an N2 phenotype (i.e., they are educated not to attack can-cer cells, but to provide cytokines that exert pro-tumor functions) (Fig. 1).1 It is believed that the switch from the N1 to the N2 phenotype (and vice versa) is mainly controlled by cytokines and chemokines.1 Immunotherapy with BCG admin-istered intravesically stimulates a potent inflammatory response with a Th1 pro-file, whereby neutrophils are recruited much earlier than other immune cells. Neutrophils are shown to be required for the efficacy of BCG immunotherapy in mouse models,2 and proportionately, neutrophils account for about 75 % of Redirecting neutrophils against bladder cancer cells by BCG and Smac mimetic combinatio